This Research Career Award application is intended to provide research experience and career development opportunities to a new investigator whose career aspiration is to advance the understanding of the epidemiology and prevention of blood-related cancers. The research focuses on multiple myeloma (MM), the etiology of which is poorly understood. The low (30%) 5-year survival of MM patients underscores the urgency of identifying modifiable risk factors. Obesity was recently reported to predict MM, and thus other correlates of energy balance such as adult weight gain and/or physical activity may also be related to MM. In addition, dysregulation of the insulin-like growth factor (IGF)-1 pathway may predict MM risk. We propose to evaluate these hypotheses in a nested matched case-control study, using combined questionnaire and biomarker data from three large prospective cohort studies: the Nurses'Health Study, the Health Professionals'Follow-up Study, and the Women's Health Study. We project a pooled sample size of 380 cases and 760 controls, of whom 100 cases and 200 controls will have archived plasma and DMA for the biomarker analyses. We will conduct conditional logistic regression analysis to estimate the association of obesity, adult weight gain, physical activity, and prediagnostic plasma levels of IGF-1, IGF binding protein 3, acid-labile subunit and C-peptide with MM. We will also examine the association of unique haplotypes of 5 IGF-related genes with MM. These analyses will contribute the first data on the relations of these risk factors (other than obesity) with MM. The project takes advantage of the rich environment of the Channing Laboratory, the Dana-Farber/Harvard Cancer Center and its Multiple Myeloma SPORE, and the Harvard School of Public Health for both research and career development support. The training program includes coursework to strengthen skills in genetic data analysis and nutritional epidemiology;a plan for intentional mentoring by the Co-Sponsors, Drs. Graham Colditz and Kenneth Anderson, each of whom offer valuable experience and expertise;participation in local working groups and seminar series;and attendance at professional meetings. Thus, the proposed project represents an innovative research project strategically designed to enhance the career development of the Candidate.